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  • Title: Altered GABA(A)-benzodiazepine receptor number and pharmacology in the adult guinea pig cerebral cortex after chronic prenatal ethanol exposure.
    Author: Bailey CD, Brien JF, Reynolds JN.
    Journal: Alcohol Clin Exp Res; 1999 Nov; 23(11):1816-24. PubMed ID: 10591599.
    Abstract:
    BACKGROUND: The effects of chronic prenatal ethanol exposure on GABA(A)-benzodiazepine receptor number and binding pharmacology were examined in the cerebral cortex of the postnatal guinea pig. METHODS: [3H]Flunitrazepam binding to GABA(A)-benzodiazepine receptors was measured in a cerebral cortical cell membrane preparation obtained at postnatal days 11 (preweaning), 21 (postweaning), and 61 (adulthood). Zolpidem, a GABA(A)-benzodiazepine type 1 receptor-selective ligand, was used in a [3H]flunitrazepam competition study. 3a-Hydroxy-5alpha-pregnan-20-one (allopregnanolone) potentiation of [3H]muscimol and [3H]flunitrazepam binding, and GABA potentiation of [3H]flunitrazepam binding were measured in these same animals. RESULTS: At postnatal day 61, but not at the younger ages studied, the following was observed: (1) [3H]Flunitrazepam binding exhibited an increased receptor number (Bmax) and decreased affinity (increased K(D)) in the ethanol-treated offspring compared with isocaloric-sucrose (with pair-feeding) and water-treated controls; and (2) the relative proportion of GABA(A)-benzodiazepine receptors that had high-affinity binding sites for zolpidem was decreased in the ethanol-treated offspring by 31% and 38% compared with the isocaloric-sucrose/pair-fed and water-treated controls, respectively. Chronic prenatal ethanol exposure did not alter the efficiency of coupling between GABA, benzodiazepine, and neurosteroid binding sites at any postnatal ages studied. CONCLUSIONS: These results suggest that, in the cerebral cortex of the adult guinea pig, chronic prenatal exposure to ethanol results in increased GABA(A)-benzodiazepine receptor number, decreased affinity for flunitrazepam, and decreased relative proportion of the GABA(A)-benzodiazepine type 1 receptor.
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